Abstract
Introduction
Conventional studies using monolayer cell culture models for evaluating cancer treatment efficacies usually substantiated treatment effects due to neglection of the physiological and pathological effects inside the body. The use of single hormonal dose exposure to monolayer cells at a fixed duration for current hormonal studies limits the effects posed by the real physiological hormonal conditions for cancer growth in patients. This study aims to establish a simulated hormonal microenvironment culture model to mimic the hormonal changes inside body over times for better evaluation of ALA-based Photodynamic Therapy (PDT) in breast cancer.
Method
The MCF7 cells were seeded in 6-well plates with the design of a medium exchange setting. The cells were cultured for 3.5 days with continuous fluctuating sex hormones (17β-estradiol and progesterone) at the levels simulating the hormonal exposure in normal physiological microenvironment during menstrual cycles. After that, the cells were treated by Hexyl-ALA-PDT. The cellular uptake and the phototoxicity were determined by flow cytometry and MTT assay.
Results
The protoporphyrin IX (PpIX) accumulation increased 25% in the cells cultured using the model. At 4 hour incubation at 30 μM and 4J/cm2, the phototoxicity was significantly enhanced from 50% to 70% in the cells grew by the model, indicating the simulated hormonal microenvironment enhanced the Hexyl-ALA-PDT efficacy in breast cancer cells.
Conclusions
This study established a simulated hormonal microenvironment culture model for the evaluation of PDT efficacy in breast cancer. More in-depth mechanistic studies using such model shed light to explicit a closer relationship between hormones and PDT efficacy in gynecological cancers.
Acknowledgement
Hexyl-ALA was kindly provided by Photocure ASA. This study was fully supported by a grant from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (Project no.: UGC/FDS17/M06/19).
Article Info
Conventional studies using monolayer cell culture models for evaluating cancer treatment efficacies usually substantiated treatment effects due to neglection of the physiological and pathological effects inside the body. The use of single hormonal dose exposure to monolayer cells at a fixed duration for current hormonal studies limits the effects posed by the real physiological hormonal conditions for cancer growth in patients. This study aims to establish a simulated hormonal microenvironment culture model to mimic the hormonal changes inside body over times for better evaluation of ALA-based Photodynamic Therapy (PDT) in breast cancer.
Method
The MCF7 cells were seeded in 6-well plates with the design of a medium exchange setting. The cells were cultured for 3.5 days with continuous fluctuating sex hormones (17β-estradiol and progesterone) at the levels simulating the hormonal exposure in normal physiological microenvironment during menstrual cycles. After that, the cells were treated by Hexyl-ALA-PDT. The cellular uptake and the phototoxicity were determined by flow cytometry and MTT assay.
Results
The protoporphyrin IX (PpIX) accumulation increased 25% in the cells cultured using the model. At 4 hour incubation at 30 μM and 4J/cm2, the phototoxicity was significantly enhanced from 50% to 70% in the cells grew by the model, indicating the simulated hormonal microenvironment enhanced the Hexyl-ALA-PDT efficacy in breast cancer cells.
Conclusions
This study established a simulated hormonal microenvironment culture model for the evaluation of PDT efficacy in breast cancer. More in-depth mechanistic studies using such model shed light to explicit a closer relationship between hormones and PDT efficacy in gynecological cancers.
Acknowledgement
Hexyl-ALA was kindly provided by Photocure ASA. This study was fully supported by a grant from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (Project no.: UGC/FDS17/M06/19).
Article Info
| Original language | English |
|---|---|
| Pages (from-to) | S492-S493 |
| Number of pages | 2 |
| Journal | Annals of Oncology |
| Volume | 33 |
| Issue number | 6 SUPPL. |
| DOIs | |
| Publication status | Published - 1 Jul 2022 |
